Our studies indicate that virulent mycobacteria disrupt the phagosomes of normal rabbit alveolar macrophages and escape normal lysosome-phagosome mechanisms. Experiments are proposed to compare the capacities of the Ravenel and BCG strains of Mycobacterium bovis, the H37Rv and H37Ra strains of M. tuberculosis, M. smegmatis and M. phlei to disrupt the phagosomes in normal and BCG-immune alveolar macrophages. Living mycobacteria will be compared with killed organisms. The effect of specific immune serum will also be evaluated. In addition, sub-populations of normal and BCG-immune macrophages will be separated on discontinuous gradients of Percoll. Based on preliminary data it is postulated that virulent mycobacteria disrupt the phagosomes in normal alveolar macrophages but fail to do so in BCG-immune macrophages. Subsequent studies will include a comparative analysis of membranes from normal and BCG-immune alveolar macrophages and search for surface components of virulent mycobacteria that disrupt membranes from normal alveolar macrophages.